Field of the Invention
This invention relates to the structure of sample support plates for the analyses of organic samples in time-of-flight mass spectrometers with ionization of the analyte substances by matrix-assisted laser desorption, given that today's requirements in respect of the mass accuracy mean that the surface of the sample support plates must have a high degree of planarity.
Description of the Related Art
Mass spectrometry with ionization by matrix-assisted laser desorption (MALDI) has become established as a standard method for the analysis of biomolecules. Time-of-flight (TOF) mass spectrometers are usually used. They determine the mass of the ions by measuring their time of flight from the surface of the sample support plate to the ion detector.
In order to fulfill today's requirements in respect of the accuracy of the mass determination, the ions from all samples on the sample support plate must pass through flight paths whose lengths are exactly known. If one assumes that the flight path is two meters long, as is usual in commercially available mass spectrometers, this means that a deviation in the flight distance of only one micrometer results in a deviation in the time of flight of half a millionth, and a deviation in the mass calculated therefrom by one part per million (1 ppm). Today's mass determinations aim to achieve deviations of only a few hundred parts per billion, however. This means that the length of the flight path from sample to sample must be known to within one tenth of a micrometer.
Since the sample support plates are usually moved with precise x-y movement stages so that each sample under analysis is in the axis of the trajectory, the planarity of the sample support plates plays a very important role. Deviations from planarity over a wide area or slight tilting of the sample support plates can be taken into account by measuring a pattern of mass reference samples distributed over the plate, since these measurements give a pattern of the precise distances of the reference samples from the ion detector. When calculating the mass from the time of flight, however, it must be possible to do a very accurate interpolation for the analytical samples which lie between the mass reference samples. The sample support plate must therefore have no undulations (or as few as possible).
Modern time-of-flight mass spectrometers use movement stages which can mechanically eliminate any tilting of the sample support plates by measuring mass reference samples. This mechanical correction is equivalent to a linear mathematical interpolation, but a linear interpolation requires planarity of the sample support plate over a wide area without any curvature.
For preparing the samples on the sample support plate, there are methods which produce thin matrix layers with embedded analyte molecules and with a thickness of only around one micrometer, which also offer relatively good reproducibility of the thickness.
From the equivalent documents DE 101 40 499 B4, GB 2 378 755 B and U.S. Pat. No. 6,670,609 B2 (J. Franzen, 2001), composite plates are known which consist of a stainless steel plate around three to four millimeters thick on a substructure produced by injection molding or even made from a plastic material, which is not very precise in terms of shape. The planarity in the near and far region here is provided solely by the stainless steel plate. It has been found, however, that stainless steel plates of this thickness are deformed by machining (cutting and milling) and the resulting internal stresses to such a degree that they do not provide the planarity required today.
The equivalent documents DE 102 30 328 B4, GB 2 391 066 B and U.S. Pat. No. 6,825,465 B2 (M. Schürenberg, 2002) describe how an elastic, electrically conductive, thin plastic plate is fastened on a solid substructure by being clamped around its edge, the planarity being provided almost solely by the substructure. This cannot fulfill today's requirements in respect of planarity either.
The document WO 2005/037434 A1 (McCarthy et al., “MALDI Plate with Removable Magnetic Insert”) explains how a sample support plate having at least one magnetic part is held in a frame by a magnet. The planarity here must be provided solely by the sample support plate. The document U.S. Pat. No. 7,619,215 B2 (Kim et al., “Sample Plate for MALDI Mass Spectrometry and Process for Manufacture of the Same”) likewise shows magnetic fixation of a sample plate on a flat frame by means of a multitude of magnets.
In view of the foregoing, there is still a need for sample supports which offer the requisite planarity, can be produced at low cost and fulfill other requirements, if possible, for example the single-use requirement for IVD methods and the possibility to use them in pipetting robots.